Simple Synthesis of a Heterocyclophane Exhibiting Anti-c-Met Activity by Acting as a Hatch Blocking Access to the Active Site*.

A simple approach to the synthesis of heterocyclophane consisting of two 4,4'-bithiazoles has been developed in mild conditions. The heterocyclophane with two short chains was conveniently prepared by Hantzsch thiazoles synthesis using the reaction of 3-tert-butoxycarbonyl-3-azapentanethiocarboxamide with 1,4-dibromobutane-2,3-dione in methanol under reflux for only 15 min. Amino groups at the linkers of this heterocyclophane can be functionalized to give acylated and carbamate derivatives. Their properties as protein kinase inhibitors were investigated, and one of the heterocyclophanes exhibited specific anti-activity for c-mesenchymal epithelial transition factor (IC50 =603 nm), among seven types of protein kinases investigated. The computational site identification by ligand competitive saturation method was used to determine why the one heterocyclophane exhibited strong anti-activity for c-mesenchymal epithelial transition factor.

Surgical procedure for unexpected balloon burst complication during endoscopic balloon dilatation in a patient with common bile duct stones.

BACKGROUND: Endoscopic balloon dilatation (EBD) is the established treatment for common bile duct (CBD) stones. Although pancreatitis and bleeding have been reported as major complications of EBD, balloon-related complications are rarely reported in EBD. CASE PRESENTATION: A 30-year-old woman with suspected CBD stones underwent endoscopic retrograde cholangiopancreatography (ERCP) and EBD. During EBD, the balloon of the EBD catheter suddenly burst at the biliary sphincter. We therefore performed surgical intervention: removal of the broken EBD catheter and T-tube drainage. Finally, the patient was discharged without any complications. CONCLUSIONS: We present a case involving a burst balloon of an EBD catheter as a rare complication during EBD, as well as the surgical technique that was used to treat this complication.

[Two Cases of Lung Stage â ¢Squamous Cell Carcinoma Treated with Carboplatin (CBDCA)plus Nab-Paclitaxel(Nab-PTX)].

Case 1: 83 years old man. For left upper lobe lungs squamous cell carcinoma infiltrating left main pulmonary artery. After 2 courses went of carboplatin(CBDCA)(AUC: 6)+weekly nab-paclitaxel(nab-PTX)(AUC: 6)+, left upper lobectomy and ND2 lymph nodes dissection. Tumor disappeared in pathology and diagnosed of Ef. 3. Case 2: 81 years old man. Right upper lobe lungs squamous cell carcinoma in #4R lymph node metastasis with the superior vena cava invasion. After 2 courses went of CBDCA(AUC: 6)+weekly nab-PTX(100mg/m2), left upper lobectomy and ND2 lymph nodes dissection. Tumor disappeared in pathology and diagnosed of Ef. 3. Nab-PTX may be considered a preoperative chemotherapeutic agent of choice for squamous cell carcinoma.

Importance of the High-Expression of Proline Transporter PutP to the Adaptation of Escherichia coli to High Salinity.

　The effect of the amount of the proline transporter PutP expression on the mechanism of adaptation of E. coli cells to high salinity was analyzed. The PutP gene derived from the E. coli expression plasmid was introduced into the E. coli cell, and a high PutP expression strain was developed. At 1.2 M NaCl culture condition, the growth of normal E. coli cells was inhibited, whereas high ProP expression cells showed growth under 2.5 M NaCl conditions. The uptake of proline by E. coli as a compatible solute and substrate for metabolization was in good accordance with those seen in cell growth. These data suggested that the amount of the proline transporter PutP expression played an important role in the adaptation of E. coli cells to high saline conditions.

Possible utility of contrast-enhanced ultrasonography for detecting spread of local anesthetic in nerve block.

PURPOSE: This study demonstrated the effects of perfluorobutane (Sonazoid®) with contrast-enhanced ultrasonography (CEUS) to identify the spread of local anesthetics in ultrasound-guided nerve block. METHODS: This study consists of simulation, cadaveric, and animal studies. In a simulation study, 1% lidocaine with 10- to 1000-fold diluted Sonazoid®, a US-specific contrast agent to diagnose hepatic and breast cancers (0.5 mL), was injected into a resin-based phantom to determine the optimal concentration for ultrasound-guided peripheral nerve block. The enhanced area was measured by direct observation and ultrasonography (US). In the cadaver study, ultrasound-guided sciatic nerve block was performed at the popliteal fossa in the 9 extremities, and 5 mL of the optimally diluted Sonazoid® defined in the simulation study with X-ray contrast medium and blue dye was injected. Longitudinal spread of the solution was measured by CEUS, X-ray imaging and anatomical dissection. In the animal study, the optimally diluted Sonazoid® was injected around the sciatic nerve of rats (n = 6), and neuronal function and toxicity were evaluated by behavioral and histological estimation. RESULTS: The simulation study proved that 100-fold diluted Sonazoid® was the optimal concentration. In the cadaver study, CEUS and anatomical dissection (r = 0.90, P = 0.0020) or radiography (r = 0.84, P = 0.0072) showed high agreement and correlation with the longitudinal spread. CEUS clearly showed a fine intraneuronal injection image compared to the usual B-mode imaging. The animal study suggested no adverse effects by co-administration of lidocaine and Sonazoid®. CONCLUSIONS: CEUS with 100-fold diluted Sonazoid® could identify the spread of local anesthetic as well as radiography and anatomical dissection, and distinguish between intra- and extraneuronal injections without neurodegeneration.

Radioactive cesium accumulation in seaweeds by the Fukushima 1 Nuclear Power Plant accident-two years' monitoring at Iwaki and its vicinity.

Accumulations of radionuclides in marine macroalgae (seaweeds) resulting from the Fukushima 1 Nuclear Power Plant (F1NPP) accident in March 2011 have been monitored for two years using high-purity germanium detectors. Algal specimens were collected seasonally by snorkeling at Nagasaki, Iwaki, Fukushima Prefecture (Pref.), Japan, ca. 50 km perimeter from the F1NPP. Additional collections were done at Soma, Hironocho, Hisanohama and Shioyazaki in Fukushima Pref. as well as at Chiba Pref. and Hyogo Pref. as controls. In May 2011, specimens of most macroalgal species showed ¹³7Cs levels greater than 3,000 Bq kg⁻¹ at Shioyazaki and Nagasaki. The highest ¹³7Cs level recorded 7371.20 ± 173.95 Bq kg⁻¹ in Undaria pinnatifida (Harvey) Suringar on 2 May 2011, whereas seawater collected at the same time at Shioyazaki and Nagasaki measured 8.41 ± 3.21 and 9.74 ± 3.43 Bq L⁻¹, respectively. The concentration factor of marine macroalgae was estimated to be ca. 8-50, depending on taxa and considering a weight ratio of wet/dry samples of ca. 10. ¹³7Cs level declined remarkably during the following 5-6 months. In contrast, the ¹³7Cs level remained rather stable during the following 12-16 months, and maintained the range of 10-110 Bq kg⁻¹. Contamination was still detectable in many samples in March 2013, 24 months after the most significant pollution.

Thermodynamic Measurements of Alloys and Compounds by Double Knudsen Cell Mass Spectrometry and Their Application to Materials Processing.

For the development and optimization of materials processing a collection of thermodynamic information concerning substances that participate in the reactions is important. One fundamental way to obtain such information is to measure the vapor pressure of gas species under conditions where they are in equilibrium with the condensed phases. Over the past 60 years Knudsen cell mass spectrometry has been used to identify and quantitatively determine gas species at high temperatures. This article describes thermodynamic foundation and examples of measurements in order to demonstrate the use of mass spectrometry focusing on the field of process metallurgy and recycling processes.

Accumulation of radioactive cesium released from Fukushima Daiichi Nuclear Power Plant in terrestrial cyanobacteria Nostoc commune.

The Fukushima Daiichi Nuclear Power Plant accident released large amounts of radioactive substances into the environment and contaminated the soil of Tohoku and Kanto districts in Japan. Removal of radioactive material from the environment is an urgent problem, and soil purification using plants is being considered. In this study, we investigated the ability of 12 seed plant species and a cyanobacterium to accumulate radioactive material. The plants did not accumulate radioactive material at high levels, but high accumulation was observed in the terrestrial cyanobacterium Nostoc commune. In Nihonmatsu City, Fukushima Prefecture, N. commune accumulated 415,000 Bq/kg dry weight (134)Cs and 607,000 Bq kg(-1) dry weight (137)Cs. The concentration of cesium in N. commune tended to be high in areas where soil radioactivity was high. A cultivation experiment confirmed that N. commune absorbed radioactive cesium from polluted soil. These data demonstrated that radiological absorption using N. commune might be suitable for decontaminating polluted soil.

B-Z transition of (dA-T)(n) duplexes induced by a spermine porphyrin-conjugate via an intermediate DNA conformation.

The spermine conjugate of the cationic porphyrin ligand (1) selectively induced the B-Z transition of the [(dA-T)n]2 sequence at low salt concentrations. The [(dG-C)n]2 sequence was not transformed into the Z-form. The B-Z transition was induced via an intermediate DNA conformation, which was formed by the external binding and formation of an assembly of 1 onto B-DNA.

Social interaction influences blood cortisol values and brain aromatase genes in the protandrous false clown anemonefish, Amphiprion ocellaris.

Anemonefish, Amphiprion spp., are socially controlled, protandrous sex changers with a monogamous mating system. Under certain conditions, sexually immature anemonefish with ambisexual gonads differentiate directly into males or females. Formation and maintenance of social rank in a group are considered key requirements for the induction of sex change or differentiation. Generally, each animal living in a social group experiences a different level of social stress in accordance with its social rank, and we hypothesize that the stress situation of individual anemonefish influences its sex determination. Groups of three sexually immature anemonefish were placed into each of five experimental tanks and kept for 10 days to allow for social rank formation and behavioral observation. The fish were then euthanized, and blood and brain samples were collected from each fish. The social rank of each individual was distinguishable from day 1 of the experiment. Aggressive behaviors were most frequent and blood Cortisol values were higher in dominant individuals. The transcription of mRNA for stress-related genes, i.e., those encoding for glucocorticoid and arginine vasotocin receptors, was higher in the brains of dominant individuals than in other social ranks. Furthermore, we detected higher transcription levels of gonad and brain aromatase genes, which encode the enzyme that converts androgens into estrogens, in the brains of dominant individuals. These results suggest that social rank reflects the blood Cortisol value, which in turn leads to sex differentiation by manipulating transcription of genes, including aromatase genes, in the brain.

Ferulic acid esters and weight-loss promoting effects in rats.

We previously fed rats with an ester (90 ppm in a powdered AIN93G diet) synthesized from gallic acid and 1,2-dioleoyl glycerol and found that it promoted weight loss more effectively than either octyl gallate or gallic acid. Here, we esterified ferulic acid (FerA) with oleic acid, monooleoyl glycerol and dioleoyl glycerol to obtain oleoyl ferulic acid (FO), feruloyl monooleoyl glycerol (FMO) and feruloyl dioleoyl glycerol (FDO) esters, respectively. A mixture of AIN93G and 90 ppm of each ester and FerA was fed to 10-week-old male Wistar rats for 12 weeks. The FMO and FDO groups weighed less than the control group starting from approximately 16 weeks of age. At 21 and 22 weeks of age, weight significantly differed between the FMO and both groups, respectively, and controls. The FO, FerA and control groups did not significantly differ in terms of body, liver, kidney and retroperitoneal fat tissue weights and serum biochemical findings. We concluded that the hydroxyl group of FerA is essential for promoting weight loss and that the carboxyl group should be esterified with alcohol. In addition, monooleoyl glycerol and dioleoyl glycerol did not show any difference as the alcohol moiety of the ester in the weight loss effect.

Ultrasound-guided supraclavicular central venous catheterization in patients with malignant hematologic diseases.

We present two cases of central venous catheterization (CVC) in which an ultrasound-guided in-plane approach was used. Case 1 was a 60-year-old man with acute myelogenous leukemia in whom a right supraclavicular CVC was performed. He had pancytopenia (leukocytes 2,000/µL; erythrocytes 350 × 10(4)/µL; platelets 5.6 × 10(4)/µL), and abnormal coagulability (prothrombin time-international normalized ratio 1.35). A linear array transducer was positioned cephalad to the right clavicle and rotated 30° clockwise. The 21-gauge needle was manipulated from outside of the transducer. A CV catheter (CV legaforce EX(®); Terumo Co., Japan) was placed and stitched near the right clavicle. The patient felt no discomfort caused by the catheter. Case 2 was a 64-year-old women with malignant lymphoma whose right internal jugular vein was surrounded by abnormally enlarged lymph nodes. CVC was performed by the in-plane supraclavicular approach, avoiding puncture of the lymph node. This novel CVC technique is useful to minimize the risk of complications and patient discomfort by indwelling catheter.

Assays of PCB congeners and organochlorine insecticides with the transgenic Arabidopsis and tobacco plants carrying recombinant guinea pig AhR and GUS reporter genes.

Certain congeners of polychlorinated biphenyls (PCBs) and organochlorine insecticides are ligands of aryl hydrocarbon receptors (AhRs) in animals. A recombinant guinea pig (g) AhR, XgDV, was constructed by fusing the ligand-binding domain of gAhR, the DNA-binding domain of LexA, and the transactivating domain of VP16. Then, the expression unit of ß-glucuronidase (GUS) reporter gene regulated by XgDV was introduced into Arabidopsis and tobacco plants. When the transgenic Arabidopsis XgDV plants were cultured on Murashige-Skoog (MS) medium containing PCB congeners, the GUS activity in the plants increased toxic equivalent (TEQ)-dependently. The GUS activity in the transgenic Arabidopsis XgDV plants cultured on MS medium containing the organochlorine insecticide dieldrin was also induced. On the other hand, in the case of DDT, the GUS activity induced by 3-methylcholanthere in the plants decreased. The transgenic Arabidopsis XgDV plants detected 1000 ng g(-1) PCB126 in 1 g of soils. Thus the XgDV plants seemed to be useful for convenient assays of PCB congeners and organochlorine insecticides, without any extraction and purification steps.

Gallic acid glycerol ester promotes weight-loss in rats.

Lifestyle-related diseases arise from obesity in 30 - 60% of cases. In recent years, food functions controlling the nutritional physiology of lipids have been a focus of disease prevention. Animal feeding experiments have revealed that esters made from gallic acid (GA) and (-)-epigallo-catechin (EGC) or linoleyl alcohol are more effective in weight-loss promotion and metabolic syndrome management than are intact GA and EGC. In this study, an ester (DOGGA) was chemically synthesized from GA and 1,2-dioleoyl glycerol and its effect was compared to that of octyl gallate (OG) and GA in male Wistar rats fed a powdered standard diet containing 7% frying oil for 12 weeks. Results revealed remarkably low body weight gains and food efficiency ratios in the DOGGA group, and the effects of OG were less pronounced than those of DOGGA. The GA group showed no difference from the control group. In addition, fecal lipid content in the DOGGA group was statistically higher than that in the control group, although organ weights and serum biochemical analyses did not differ between the groups. In conclusion, the data suggested that DOGGA promoted weight-loss more effectively than OG and GA did and that the alcohol moiety of gallate is not necessarily EGC and linoleyl alcohol.

Visualization and structural analysis of the bacterial magnetic organelle magnetosome using atomic force microscopy.

The unique ability of magnetotactic bacteria to navigate along a geomagnetic field is accomplished with the help of prokaryotic organelles, magnetosomes. The magnetosomes have well-ordered chain-like structures, comprising membrane-enveloped, nano-sized magnetic crystals, and various types of specifically associated proteins. In this study, we applied atomic force microscopy (AFM) to investigate the spatial configuration of isolated magnetosomes from Magnetospirillum magneticum AMB-1 in near-native buffer conditions. AFM observation revealed organic material with a approximately 7-nm thickness surrounding a magnetite crystal. Small globular proteins, identified as magnetosome-associated protein MamA, were distributed on the mica surface around the magnetosome. Immuno-labeling with AFM showed that MamA is located on the magnetosome surface. In vitro experiments showed that MamA proteins interact with each other and form a high molecular mass complex. These findings suggest that magnetosomes are covered with MamA oligomers in near-native environments. Furthermore, nanodissection revealed that magnetosomes are built with heterogeneous structures that comprise the organic layer. This study provides important clues to the supramolecular architecture of the bacterial organelle, the magnetosome, and insight into the function of the proteins localized in the organelle.

Multiple abdominal granuloma caused by spilled gallstones with imaging findings that mimic malignancy.

Multiple abdominal granulomas caused by spilled gallstones during a laparoscopic cholecystectomy are a rare complication. The images of the granuloma mimicked malignancy.

Social rank modulates brain arginine vasotocin immunoreactivity in false clown anemonefish (Amphiprion ocellaris).

The brain nanopeptide arginine vasotocin (AVT) and its mammalian homolog arginine vasopressin are involved in the regulation of social and reproductive behavior. We investigated the relationship between social rank formation and the brain AVT system in the false clown anemonefish (Amphiprion ocellaris), which forms a social rank that leads to sex differentiation in higher-ranked individuals. Tanks of three sexually immature fish were kept for 90 days and each fish's behavior was observed once a month. The social rank of each individual was distinguishable by behavior, but gonadosomatic index (GSI) did not differ significantly. The number of AVT neurons in the magnocellular layer in the preoptic area (POA) increased in subordinate individuals and declined with increasing hierarchical dominance. These results suggest that social rank formation modulates AVT production in the brain of the clown anemonefish and may influence their later sex differentiation.

Effect of moderate salinity stress treatment on the stimulation of proline uptake and growth in Escherichia coli CSH4 and its mutants under high salinity.

Activity of proline uptake in Escherichia coli CSH4 was inhibited in the presence of 1 M NaCl, while it was recovered if the cells were incubated at 30 degrees C for 1 h in a moderate salinity stress (MSS) solution which consists of Davis minimal medium with 5 mM proline and 0.5 M NaCl. Then, an attempt was made to examine whether MSS treatment is also effective on the activity restoration of proline uptake and growth under high salinity for E. coli CSH4 mutants with different combinations of proP, putA, putP, and proU which are related to the transport and metabolization of proline. After MSS treatment, proline uptake was vigorously occurred for the mutants with proline transporter gene proP but not for its deficient ones. For the expression of proline uptake activities of these mutant strains after MSS treatment, PO(4)(3-) in MSS solution is more important than K(+). No growth of strain CSH4 and its mutants without MSS treatment was observed, when cultured in high osmotic medium G (0.8 M NaCl) consisting of 1 mM glycine betaine and Davis minimal medium without potassium phosphate supplemented. After MSS treatment, however, mutant strains lacking proP showed sufficient growth in medium G. Cell growth of proP(+) strains was recognized if MSS treatment was performed in the absence of proline. In conclusion, growth of mutant strains under high-salinity medium G depended on their amount of proline accumulated during MSS treatment, in which K(+) and PO(4)(3-) might play a key role to guarantee their sufficient growth.

Bioassay of estrogenic compounds in transgenic Arabidopsis plants carrying a recombinant human estrogen receptor gene and a GFP reporter gene.

Transgenic Arabidopsis plants carrying a recombinant human estrogen receptor gene and a green fluorescent protein reporter gene were used to bioassay estrogenic compounds. We constructed four recombinant human estrogen receptor genes by combining the DNA-binding domain of LexA, a synthetic nuclear localization signal, a ligand-binding domain of the human estrogen receptor, and a transactivation domain of VP16 in different orders; the XEV plants were the most sensitive, and were able to detect 0.001 ng ml(-1) of 17ss-estradiol (E(2)). The transgenic plants absorbed E(2) and 4-nonylphenol present in the nutrient solution, whereas most of the other compounds seemed to be retained in, or on, the roots. Estrone, methoxychlor, bisphenol A, 4-nonylphenol, and 4-t-octylphenol in the medium were clearly detected by RT-PCR and PCR of the genomic DNA. The transgenic Arabidopsis XEV plants thus have potential for the bioassay of estrogenic compounds.

Social environment and sex differentiation in the false clown anemonefish, Amphiprion ocellaris.

Plasticity in sex differentiation is known to be common in teleost fishes. Anemonefishes are protandrous; females are the largest and dominant members of social groups, displaying frequent aggressive behavior towards other members of groups. The second-ranked individuals become males and others remain as non-reproductive individuals. Here we examine the influence of social interaction in-group on sex differentiation in the false clown anemonefish, Amphiprion ocellaris, under laboratory conditions. Three juvenile anemonefish were kept in a tank for 180 days and their behaviors observed once a month. The social rank of individuals was distinguishable by their interactions in a group, with rank order clearly correlated with aggressive and appeasing behaviors. The dominant individuals occupied the shelter in the tank from the start to completion of the observation period. The body mass of dominant individuals increased compared to group-housed control fish, while third-ranked individuals showed growth suppression. The ratio of testicular tissue in gonads increased in dominant and second-ranked individuals but decreased in the third-ranked individuals. Differences in the plasma concentrations of estradiol, testosterone, and cortisol were not significant, but the concentration of 11-ketotestosterone was significantly higher in dominant individuals. These results suggest that, in false clown anemonefish, reproductive suppression of lower-ranked individuals becomes apparent in the first stage of group formation, and sex differentiation of upper-ranked individuals is gradually determined by long-term social interactions.